Several oncogenic pathways are typical overexpressed and activated in pancreatic cancer, which include AKT, Signal Transducer and Activator of Transcription 3 (STAT3), Notch-1, and NF-?B. An effective therapeutic agent may need to exhibit the capacity to inhibit these pathways. STAT3, Notch-1, NF-?B, and AKT pathways are among the major oncogenic pathways activated in pancreatic cancer. These four oncogenic pathways are considered to play critical roles in growth, survival, invasion, angiogenesis, and other functions in pancreatic cancer and thereby emerged as attractive therapeutic targets for this cancer. We proposed to evaluate the inhibitory efficacy of GO-Y030, a new and more potent analogue of the dietary agent, curcumin. Our preliminary results in this proposal demonstrated for the first time that GO-Y030 is approximately 26-397 times more potent than curcumin in inhibiting pancreatic cancer cell viability as well as more potent than cu cell lines. We will also examine whether the expression of STAT3, AKT, and Notch-1 can rescue the inhibitory effects of GO-Y030 in pancreatic cancer cells. In specific aim 2, we will evaluate the inhibitory efficacy of GO-Y030 to suppress PANC-1, MIA-PACA-2, and BxPC-3 pancreatic cancer cells in orthotopic tumor model. Pancreatic cancer is one of the most serious types of cancer and there is a critical need to develop more effective therapeutic agents for pancreatic cancer. Our proposed studies, if successful, will provide a promising potential using GO-Y030 as a novel therapeutic agent for pancreatic cancer with the ultimate goal to reduce the mortality of pancreatic cancer and extending the quality of healthy life for people in this country and around the world. PUBLIC HEALTH RELEVANCE: Each year about 32,000 individuals in the United States are diagnosed with pancreatic cancer. Cancer of the exocrine pancreas is rarely curable and has an overall survival rate of less than 4%. The. [unreadable]itical need for better treatment approaches for pancreatic cancer. The objectives of this proposal are to evaluate the inhibitory efficacy of a new and highly potent curcumin analogue, GO-Y030 in human pancreatic cancer cells in vitro and in a mouse orthotopic tumor model. 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